title: Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll-like receptors 2 and 4.
abstract: Lactoferrin, a key component of innate immunity, is a cationic monomeric 80-kDa glycoprotein of the transferrin superfamily. Recombinant human lactoferrin, known as talactoferrin (TLF), induces a distinct functional maturation program in human dendritic cells (DCs) derived from peripheral blood monocytes. However, the receptors and molecular mechanisms involved in this induction have not been fully determined. By exploiting genome-wide transcription profiling of immature DCs, TNF-α- and IL-1β-matured DCs (m-DCs), and TLF-matured DCs (TLF-DCs), we have detected a set of transcripts specific for m-DCs and one specific for TLF-DCs. Functional network reconstruction highlighted, as expected, the association of m-DC maturation with IL-1β, TNF-α, and NF-κB, whereas TLF-DC maturation was associated with ERK and NF-κB. This involvement of ERK and NF-κB transduction factors suggests direct involvement of Toll-like receptors (TLRs) in TLF-induced maturation. We have used MyD88 inhibition and siRNA silencing TLRs on human DCs and mouse TLR-2-knockout cells, to show that TLF triggers the maturation of both human and mouse DCs through TLR-2 and TLR-4.
authors.affiliation: 1Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, via Nizza 52, Torino 10126, Italy. federica.cavallo@unito.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Spadaro
authors.forename: Monica
authors.initials: M
authors.lastname: Montone
authors.forename: Maddalena
authors.initials: M
authors.lastname: Arigoni
authors.forename: Daniela
authors.initials: D
authors.lastname: Cantarella
authors.forename: Guido
authors.initials: G
authors.lastname: Forni
authors.forename: Federica
authors.initials: F
authors.lastname: Pericle
authors.forename: Steve
authors.initials: S
authors.lastname: Pascolo
authors.forename: Raffaele A
authors.initials: RA
authors.lastname: Calogero
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007781:Lactoferrin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051198:Toll-Like Receptor 5 / Q000378:metabolism
chemical_list: D053594:Myeloid Differentiation Factor 88; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D007781:Lactoferrin
keywords: alarmins; pattern recognition receptors